Bortezomib with Dexamethasone compared with oral melphalan and predonisone pluse bortezomib in patients with refractory multiple myeloma: randomized phase 2 study

INTERVENTION: Patients newly diagnosed multiple myeloma will receive melphalan and predonisolone(MP) for 3 cycles. MP therapy consists of oral administration of melphalan at 9mg/m2 on day 1‐4 and oral predonisolone at 60mg/m2 on day1‐4. Each cycle will be repeated for every 6 weeks. After 3 cycles, patients, whose response will be less than PR, will be randomly allocated to bortezomib with dexamethazone(BD) or MP pluse bortezomib(MPV). BD arm consists with BD therapy and weekly BD therapy. In BD therapy, bortezomib 1.3mg/m2 will be administered intravenously on days 1, 4, 8, 11, 22, 25, 29, and 32. And dexamethasone 20mg/m2 will be administered on days 1, 2, 4, 5, 8, 9, 11, 12, 22, 23, 25, 26, 29, 30, 32, and 33. In weekly BD therapy, bortezomib 1.3mg/m2 will be administered intravenously on days 1, 8, 22, and 29. And dexamethasone 20mg/m2 will be administered on days 1, 2, 8, 9, 22, 23, 29, and 30. Patients will receive BD therapy for 2 cycles and weekly BD therapy for 5 cycles. Each cycle will be repeated every 6 weeks MPV arm consists with MPV therapy and weekly MPV therapy. In MPV therapy, bortezomib 1.3mg/m2 will be administered intravenously on days 1, 4, 8, 11, 22, 25, 29, and 32 with MP therapy. In weekly BD therapy, bortezomib 1.3mg/m2 will be administered intravenously on days 1, 8, 22, and 29 with MP therapy. Each cycle will be repeated every 6 weeks CONDITION: myeloma PRIMARY OUTCOME: Overall response rate SECONDARY OUTCOME: TTP; OS; PFS; CR rate; Time to response; Duration of response; Safety INCLUSION CRITERIA: 1.have given written informed consent. 2.have had diagnosis of symptomatic/non secretary myeloma by IMWG criteria. Or have had diagnosis of myeloma. 3.have measurable lesion. Secretary type: have measurable serum M protein or urine M protein Non secretary type: have measurable lesion > = 2.0 cm in major axes. 4.aged more than 65 years old or aged from 20 to 65 who cannot be candidate for autologous sten cell transplantation. 5.Performance status (ECOG) of 0 to 2 6.Refractory after 3 courses of MP therapy. Refractory is defined as patients whose response is less than PR. 7.Patients with adequately maintained organs functions. A)T‐bil, AST, ALT =< 2 times the upper limit of the institution's normal range. B)WBC >= 3000/ul(neutrophil >= 1500/ul), PLT >= 50000/ul, Hb >= 8g/dl C)ejection fraction >=50% D)SatO2 >=94% E)peripheral neuropathy =< grade 1